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Cited by 53Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes and associated disorders

Insulin and Amylin Release Are Both Diminished in First-Degree Relatives of Subjects With Type 2 Diabetes

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Knowles, Negar G., Landchild, Melinda A., Fujimoto, Wilfred Y., Kahn, Steven E.·2002·Diabetes Care
DOI 10.2337/diacare.25.2.292
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Abstract

OBJECTIVE—To determine whether first-degree relatives of individuals with type 2 diabetes, who are at high risk of subsequently developing hyperglycemia, manifest alterations in β-cell function including an alteration in the co-release of insulin and amylin. RESEARCH DESIGN AND METHODS—In 30 first-degree relatives and 24 matched subjects with no family history of diabetes, β-cell function was measured as the intravenous glucose-induced acute insulin response (AIRg) and acute amylin response (AARg). The insulin sensitivity index (SI) was quantified and used to account for the role of insulin sensitivity to modulate β-cell function (SI × β-cell function). RESULTS—Fasting plasma glucose (5.3 ± 0.1 vs. 5.1 ± 0.1 mmol/l; means ± SEM), immunoreactive insulin (IRI) (68 ± 7 vs. 57 ± 6 pmol/l) and amylin-like immunoreactivity (ALI) (5.5 ± 0.6 vs. 4.7 ± 0.7 pmol/l) were similar in relatives and control subjects, respectively. Relatives were insulin resistant compared with control subjects (SI: 4.86 ± 0.63 vs. 7.20 ± 0.78 × 10−5 min−1 · pmol−1 · l−1, P = 0.01), but their AIRg (392 ± 59 vs. 386 ± 50 pmol/l) and AARg (5.9 ± 0.9 vs. 6.1 ± 0.8 pmol/l) did not differ. When β-cell function was determined relative to insulin sensitivity, in the first-degree relatives, both AIRg (SI × AIRg: 1.60 ± 0.23 vs. 2.44 ± 0.31 × 10−2 min−1, P < 0.05) and AARg (SI × AARg: 2.39 ± 0.35 vs. 4.06 ± 0.56 × 10−4 min−1, P < 0.05) were reduced. The molar proportion of ALI to IRI was not altered in high-risk subjects (1.75 ± 0.16 vs. 1.71 ± 0.15%). CONCLUSIONS—First-degree relatives of subjects with type 2 diabetes have diminished β-cell function at a time when they are not hyperglycemic, and this reduction affects insulin and amylin responses proportionally. Thus, an altered amylin-to-insulin ratio is not likely to identify individuals at high risk of developing type 2 diabetes.

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  • The majority of subjects who have two first-degree relatives with Type 2 diabetes have percentile scores below the 50th percentile for the relationship between insulin sensitivity and insulin secretion.

    “Using this approach, the majority of subjects who have two first-degree relatives with Type 2 diabetes have percentile scores that place them below the mean (50 th percentile) for the relationship between insulin sensitivity and insulin secretion, which is in keeping with their high risk status [106] (Fig. 4).”

    From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [106]

  • The same parallelism between insulin and IAPP is present in humans in response to glucose and arginine over a broad range of glucose concentrations, with IAPP release being reduced in Type 2 diabetes.

    “This same parallelism is present in humans in response to both glucose [106, 118] and arginine over a broad range of glucose concentrations [119] with IAPP release being reduced in Type 2 diabetes [84, 85, 86, 87].”

    From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [106]

  • In older subjects and first-degree relatives of subjects with Type 2 diabetes, the IAPP response to glucose injection is reduced.

    “We have confirmed this hypothesis in assessments of older subjects and first-degree relatives of subjects with Type 2 diabetes in whom a reduced IAPP response to glucose injection has been shown [106, 118].”

    From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [106]

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Authors
Knowles, N. G., Landchild, M. A., Fujimoto, W. Y., & Kahn, S. E.
Affiliations
University of Washington (US)
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2002-02-01
Volume
25
Issue
2
Pages
292-297
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/diacare.25.2.292
OpenAlex
W2150981747
Cited by
51
References
49
Citations by year
2024: 3 · 2023: 1 · 2021: 2 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 1 · 2012: 2
FWCI
3.20
Type
journal article
Language
en
Open access
Locations
  • Diabetes Care (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Diabetes Association
  • U.S. Department of Veterans Affairs
  • American Federation for Aging Research
  • Amylin Pharmaceuticals
  • Office of Research and Development
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK050703, K24DK002654, DK50703, DK 02654, DK-17047, P30DK017047)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
type 2 diabetes, first-degree relatives, amylin, insulin, beta-cell function, insulin sensitivity, acute insulin response, insulin resistance, glucose tolerance, family history of diabetes, pancreatic islets, islet transplantation
MeSH terms
Adult, Amyloid, Blood Glucose, Diabetes Mellitus, Type 2, Family, Fasting, Female, Glucose Tolerance Test, Humans, Insulin, Islets of Langerhans, Male, Middle Aged, Risk Factors, Biomarkers, Linear Models, Islet Amyloid Polypeptide

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